The gut microbiome may contribute to susceptibility to developing alcoholic liver disease

Alcoholic liver disease (ALD) is a major public health issue, yet the underlying mechanisms between ethanol consumption and injury to the liver are poorly understood.  Alcoholics vary in their susceptibility to developing ALD and alcoholic hepatitis (AH) despite consuming similar amounts of alcohol.  Taken together, this evidence suggests that other factors contribute to the onset and progression of ALD other than direct toxicity of alcohol.  Intestinal inflammation and pro-inflammatory bacterial products have also been observed in ALD patients and preclinical mice models, and intestinal dysbiosis has been observed in patients with alcohol dependency.  With this in mind, a team of European researchers devised a strategy to demonstrate microbiome dysbiosis as a casual driver of liver injury. 

The researchers transplanted human gut microbiota into germ-free mice, and the mice were then placed on a high-alcohol diet.  Microbiota were harvested from human alcoholic patients with or without AH (or low severity AH).  Mice transplanted with AH-microbiota had marked increases in symptoms of liver disease as compared to those mice that received microbiota transplants from non-AH alcoholic patients.  These include severe liver inflammation (including increases in T lymphocytes and natural killer cells), more necrosis in the liver, and higher intestinal permeability.  Enterobacteria counts were high in sever-AH patients and faecalibacterium genus was associated with AH-microbiota with low severity.  In an interesting spin, the researchers also transferred microbiota from an alcoholic patient without AH to mice with liver lesions.  Interestingly, mice who had received these microbiota displayed a reduction in serum alanine aminotransferase levels and a decrease in liver regeneration, suggesting that these microbiota could even possibly reverse alcohol-induced liver lesions. 

These findings not only support an association between the gut microbiome and susceptibility to developing alcoholic liver disease, but also provide evidence that these bacteria may drive disease onset.  These were important findings that support microbiota-causal effect rather than dysbiosis as a consequence of liver disease.  This data could perhaps promote development of novel diagnostic techniques that assess the gut microbiome or bacterial metabolites of alcoholic patients.  Methods such as manipulating the microbiome as a therapeutic approach for these patients could also be explored. 

Microbiome bacteria help cancer cells evade the immune system

Optical microscope image of bacteria from the genus Fusobacteria.

A few weeks ago Kris Campbell wrote about the microbiome’s association with colorectal cancer.  This association is complex, but perhaps critically important, and last week a new study reinforced this connection.  Researchers, primarily from Israel, published results in Cell Immunity that showed common microbiome bacteria are protecting cancer cells by helping the cancer cells evade the immune system.

The researchers noticed that a type of bacteria, Fusobacterium nucleatum, which is normally found in the oral microbiome and is a cause of periodontal disease, can be found in high concentrations around colorectal tumors.  In addition, these same bacteria had been linked to various microbiome associated diseases, such as preterm birth and rheumatoid arthritis.  They suspected that these bacteria may somehow be protecting the cancer cells from the immune system, so they performed a series of experiments to find out.

The scientists grew cancer cells in the presence and absence of the F. nucleatum and then exposed these cancers to immune system cells that are designed to attack cancers.  They noticed that those cancer cells that had been grown with the bacteria were naturally protected from these immune cells.  Through a series of tests they discovered that the bacteria produce a protein called Fap2 that naturally bound with the immune cells and essentially deactivated them (technically speaking, Fap2 bound to the Natural Killer cells’ TIGIT inhibitory receptors).  Interestingly, this TIGIT receptor is nearly ubiquitous across many types of immune system cells, which means that this bacteria, and others like it, may be especially good at protecting themselves and other cancer cells from our bodies’ natural defenses.

It may be surprising for our readers to hear that bacteria are sometimes used to destroy cancer cells, like in the case of bladder cancer, but this paper shows a more dichotomous relationship between the microbiome and cancer.  While some bacteria may be helpful in killing cancers others may be helping them grow.  Either way, one thing is clear, the microbiome and cancers are intimately related, and learning about the microbiome should lead to advanced therapies for treating cancers.